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* Department of Functional Biology, Area of Immunology, Universidad de Oviedo, and
Department of Immunology, Hospital Central de Asturias, Oviedo, Spain
After TCR cross-linking, naive
CD4+CD45RA+ T cells switch to the expression of
the CD45RO isoform and acquire effector functions. In this study we
have shown that cAMP-elevating agents added to anti-CD3- and
anti-CD28-stimulated cultures of T lymphocytes prevent acquisition
of the CD45RO+ phenotype and lead to the generation of a
new subpopulation of primed CD4+CD45RA+
effector cells (cAMP-primed CD45RA). These cells displayed a low
apoptotic index, as the presence of dibutyryl cAMP (dbcAMP)-rescued
cells from CD3/CD28 induced apoptosis. Inhibition of CD45 splicing by
dbcAMP was not reverted by addition of exogenous IL-2. cAMP-primed
CD45RA cells had a phenotype characteristic of memory/effector T
lymphocytes, as they showed an up-regulated expression of CD2, CD44,
and CD11a molecules, while the levels of CD62L Ag were down-regulated.
These cells also expressed the activation markers CD30, CD71, and HLA
class II Ags at an even higher level than CD3/CD28-stimulated cells in
the absence of dbcAMP. In agreement with this finding, cAMP-primed
CD45RA cells were very efficient in triggering allogenic responses in a
MLR. In addition, cAMP-primed CD45RA cells produce considerable amounts
of the Th2 cytokines, IL-4, IL-10, and IL-13, whereas the production of
IFN-
and TNF-
was nearly undetectable. The elevated production of
IL-13 by neonatal and adult cAMP-primed CD45RA cells was specially
noticeable. The cAMP-dependent inhibition of CD45 splicing was not
caused by the production of immunosuppressor cytokines. These results
suggest that within the pool of CD4+CD45RA+
cells there is a subpopulation of effector lymphocytes generated by
activation in the presence of cAMP-elevating
agents.
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